The aim of the proposed research is to discover the biochemical mechanisms by which severe ethanol intoxication or the presence of high levels of catecholamines in the body cause cardiomyopathies. The specific goals of this project are to determine the effects of ethanol and of catecholamines on the activities and release of cardiac lysosomal hydrolases. It is hypothesized (a) that catecholamine-induced cardiac necrosis may be caused by the destructive actions of cardiac lysosomal enzymes released as a consequence of the effects of high concentrations of catecholamines on the heart, and (b) that alcoholic cardiomyopathy may similarly be due to the actions of freed lysosomal enzymes resulting from the liberation of large quantities of endogenous catecholamines during severe alcohol intoxication. Determinations will be made of the effects of acute and chronic alcohol intoxication and of catecholamine administration on the release and activities of cardiac lysosomal enzymes in rats. The in vivo effects of ethanol intoxication on blood catecholamine levels over a prolonged period of time, of beta-adrenergic blocking agents on ethanol-induced changes in cardiac lysosomal enzymes, and of lysosomal membrane-labilizing and stabilizing agents on lysosomal changes induced by ethanol and catecholamines, will be examined. In vitro studies on the effects of decreasing pH, ethanol, and catecholamines on cardiac lysosomal membrane permeability will also be carried out.